diff --git a/CHANGELOG.md b/CHANGELOG.md
index bb74fac7..f97f6e21 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -1,5 +1,7 @@
 # 0.1.2 2024-XX-XX
 
+- Reduce memory requirement for encoding genotypes with large sample sizes
+
 - Transpose default chunk sizes to 1000 variants and 10,000 samples (issue:300)
 
 - Add chunksize options to mkschema (issue:294)
diff --git a/bio2zarr/vcf2zarr/vcz.py b/bio2zarr/vcf2zarr/vcz.py
index 566f6bc7..742e9f61 100644
--- a/bio2zarr/vcf2zarr/vcz.py
+++ b/bio2zarr/vcf2zarr/vcz.py
@@ -382,7 +382,7 @@ def fixed_field_spec(
                 continue
             array_specs.append(spec_from_field(field))
 
-        if gt_field is not None:
+        if gt_field is not None and n > 0:
             ploidy = max(gt_field.summary.max_number - 1, 1)
             shape = [m, n]
             chunks = [variants_chunk_size, samples_chunk_size]
@@ -832,6 +832,7 @@ def encode_partition(self, partition_index):
                 self.encode_array_partition(array_spec, partition_index)
         if self.has_genotypes():
             self.encode_genotypes_partition(partition_index)
+            self.encode_genotype_mask_partition(partition_index)
         if self.has_local_alleles():
             self.encode_local_alleles_partition(partition_index)
             self.encode_local_allele_fields_partition(partition_index)
@@ -881,14 +882,10 @@ def encode_array_partition(self, array_spec, partition_index):
         self.finalise_partition_array(partition_index, ba)
 
     def encode_genotypes_partition(self, partition_index):
-        # FIXME we should be doing these one at a time, reading back in the genotypes
-        # like we do for local alleles
+        partition = self.metadata.partitions[partition_index]
         gt = self.init_partition_array(partition_index, "call_genotype")
-        gt_mask = self.init_partition_array(partition_index, "call_genotype_mask")
         gt_phased = self.init_partition_array(partition_index, "call_genotype_phased")
 
-        partition = self.metadata.partitions[partition_index]
-
         source_field = self.icf.fields["FORMAT/GT"]
         for value in source_field.iter_values(partition.start, partition.stop):
             j = gt.next_buffer_row()
@@ -899,13 +896,25 @@ def encode_genotypes_partition(self, partition_index):
             icf.sanitise_value_int_1d(
                 gt_phased.buff, j, value[:, -1] if value is not None else None
             )
-            # TODO check is this the correct semantics when we are padding
-            # with mixed ploidies?
-            j = gt_mask.next_buffer_row()
-            gt_mask.buff[j] = gt.buff[j] < 0
 
         self.finalise_partition_array(partition_index, gt)
         self.finalise_partition_array(partition_index, gt_phased)
+
+    def encode_genotype_mask_partition(self, partition_index):
+        partition = self.metadata.partitions[partition_index]
+        gt_mask = self.init_partition_array(partition_index, "call_genotype_mask")
+        # Read back in the genotypes so we can compute the mask
+        gt_array = zarr.open_array(
+            store=self.wip_partition_array_path(partition_index, "call_genotype"),
+            mode="r",
+        )
+        for genotypes in core.first_dim_slice_iter(
+            gt_array, partition.start, partition.stop
+        ):
+            # TODO check is this the correct semantics when we are padding
+            # with mixed ploidies?
+            j = gt_mask.next_buffer_row()
+            gt_mask.buff[j] = genotypes < 0
         self.finalise_partition_array(partition_index, gt_mask)
 
     def encode_local_alleles_partition(self, partition_index):
diff --git a/tests/test_icf.py b/tests/test_icf.py
index b59ae1dd..088be7ab 100644
--- a/tests/test_icf.py
+++ b/tests/test_icf.py
@@ -91,6 +91,19 @@ def test_INFO_NS(self, icf):
         assert icf["INFO/NS"].values == [None, None, 3, 3, 2, 3, 3, None, None]
 
 
+class TestWithGtHeaderNoGenotypes:
+    data_path = "tests/data/vcf/sample_no_genotypes_with_gt_header.vcf.gz"
+
+    @pytest.fixture(scope="class")
+    def icf(self, tmp_path_factory):
+        out = tmp_path_factory.mktemp("data") / "example.exploded"
+        return vcf2zarr.explode(out, [self.data_path])
+
+    def test_gts(self, icf):
+        values = icf["FORMAT/GT"].values
+        assert values == [None] * icf.num_records
+
+
 class TestIcfWriterExample:
     data_path = "tests/data/vcf/sample.vcf.gz"
 
diff --git a/tests/test_vcf_examples.py b/tests/test_vcf_examples.py
index c1cb2ae8..3692fe44 100644
--- a/tests/test_vcf_examples.py
+++ b/tests/test_vcf_examples.py
@@ -508,6 +508,19 @@ def test_ok_without_local_alleles(self, ds):
         nt.assert_array_equal(ds.call_genotype.values, [[[0, 0, 0]]])
 
 
+class TestWithGtHeaderNoGenotypes:
+    data_path = "tests/data/vcf/sample_no_genotypes_with_gt_header.vcf.gz"
+
+    @pytest.fixture(scope="class")
+    def ds(self, tmp_path_factory):
+        out = tmp_path_factory.mktemp("data") / "example.vcf.zarr"
+        vcf2zarr.convert([self.data_path], out, worker_processes=0)
+        return sg.load_dataset(out)
+
+    def test_gts(self, ds):
+        assert "call_genotype" not in ds
+
+
 class Test1000G2020Example:
     data_path = "tests/data/vcf/1kg_2020_chrM.vcf.gz"